ON USING PEOPLE MERELY AS A MEANS IN CLINICAL RESEARCH

It is often argued that clinical research should not violate the Kantian principle that people must not be used merely as a means for the purposes of others. At first sight, the practice of clinical research itself, however, seems to violate precisely this principle: clinical research is often beneficial to future people rather than to participants; even if participants benefit, all things considered, they are exposed to discomforts which are absent both in regular care for their diseases and in other areas of daily life. Therefore, in this paper we will consider whether people are used merely as a means by being enrolled in clinical research. On the basis of recent studies of Kantian scholars we will argue that clinical research is compatible with the Kantian principle if the conditions of possible consent and end‐sharing have been met. Participants are not used merely as a means if they have sufficient reasons to consent to being enrolled in clinical research and can share the ends of the researchers who use them. Moreover, we will claim that even if people are used merely as a means by participating in clinical research, it may not always be morally wrong to use them in this way.     

Bystanders,risks, and consent

This paper considers the moral status of bystanders affected by medical research trials. Recent proposals advocate a very low threshold of permissible risk imposition upon bystanders that is insensitive to the prospective benefits of the trial, in part because we typically lack bystanders' consent. I argue that the correct threshold of permissible risk will be sensitive to the prospective gains of the trial. I further argue that one does not always need a person's consent to expose her to significant risks of even serious harm for the sake of others. That we typically need the consent of participants is explained by the fact that trials risk harmfully using participants, which is very hard to justify without consent. Bystanders, in contrast, are harmed as a side-effect, which is easier to justify. I then consider whether the degree of risk that a trial may impose on a bystander is sensitive to whether she is a prospective beneficiary of that trial.     

XENOTRANSPLANTATION, CONSENT AND INTERNATIONAL JUSTICE

The risk posed to the community by possible xenozoonosis after xenotransplantation suggests that some form of 'community consent' is required before whole organ animal-to-human xenotransplantation should take place. I argue that this requirement places greater obstacles in the path of ethical xenotransplantation than has previously been recognised. The relevant community is global and there are no existing institutions with democratic credentials sufficient to establish this consent. The distribution of the risks and benefits from xenotransplantation also means that consent is unlikely to be forthcoming. Proceeding on the basis of hypothetical consent to a package of global health measures that includes xenotransplantation, as Rothblatt has recently advocated, is more problematic than she acknowledges. Given that it may place the lives of citizens of poor nations at risk to benefit the citizens of wealthy nations, xenotransplantation raises significant questions of international justice.     

Lay concepts in informed consent to biomedical research: the capacity to understand and appreciate risk

Persons generally must give their informed consent to participate in research. To provide informed consent persons must be given information regarding the study in simple, lay language. Consent must be voluntary, and persons giving consent must be legally competent to consent and possess the capacity to understand and appreciate the information. This paper examines the relationship between the obligation to disclose information regarding risks and the requirement that persons have the capacity to understand and appreciate the information. There has been insufficient attention to the extent to which persons must be able to understand and appreciate study information in order to have their consent deemed valid when the information is provided in simple, lay language. This paper argues that (1) the capacity to understand and appreciate information that should be deemed necessary to give valid consent should be defined by the capacity of the typical, cognitively normal adult and (2) the capacity of the typical, cognitively normal adult to understand and appreciate the concept of risk is limited. Therefore, (3) all things being equal, potential subjects must possess a limited capacity to understand and appreciate risk to be deemed competent to consent to research participation. (4) In some cases investigators ought to require that persons possess a greater than typical capacity to understand and appreciate risk.     

Does benefit justify research with children?

The inclusion of children in research gives rise to a difficult ethical question: What justifies children's research participation and exposure to research risks when they cannot provide informed consent? This question arises out of the tension between the moral requirement to obtain a subject's informed consent for research participation, on the one hand, and the limited capacity of most children to provide informed consent, on the other. Most agree that children's participation in clinical research can be justified. But the ethical justification for exposing children to research risks in the absence of consent remains unclear. One prevalent group of arguments aims to justify children's risk exposure by appealing to the concept of benefit. I call these ‘benefit arguments’. Prominent versions of this argument defend the idea that broadening our understanding of the notion of benefit to include non‐medical benefits (such as the benefit of a moral education) helps to justify children's research participation. I argue that existing benefit arguments are not persuasive and raise problems with the strategy of appealing to broader notions of benefit to justify children's exposure to research risk.     

Failla memorial lecture. Risk, research, and radiation protection

Radiation protection concerns the risk of stochastic late effects, especially cancer, and limits on radiation exposure both occupationally and for the public tend to be based on these risks. The risks are determined, mainly by expert committees, from the steadily growing information on exposed human populations, especially the survivors of the atomic bombs dropped in Japan in 1945. Risks of cancer estimated up to the early 1980s were in the range 1 to 5 X 10(-2)/Sv, but recent revisions in the dosimetry of the Japanese survivors and additional cycles of epidemiological information suggest values now probably at the high end of this range. These are likely to require an increase in the values used for radiation protection. A major problem with risk estimation is that data are available only for substantial doses and must be extrapolated down to the low-dose region of interest in radiation protection. Thus the shape of the dose-response curve is important, and here we must turn to laboratory research. Of importance are studies involving (1) dose rate, which affects the response to low-LET radiation and often to high-LET radiation as well; (2) radiation quality, since the shapes of the dose-response curves for high- and low-LET radiation differ and thus the RBE, the ratio between them, varies, reaching a maximum value RBEM at low doses; and (3) modifiers of the carcinogenic response, which either enhance or reduce the effect of a given dose. Radiation protection depends both on risk information, and especially also on comparisons with other occupational and public risks, and on research, not only for extrapolations of risk to low doses but also in areas where human information is lacking such as in the effects of radiation quality and in modifications of response.     

Research involving prisoners: consensus and controversies in international and European regulations

This article examines international and European regulations on research involving prisoners for consensus, differences, and their consequences, and offers a critical evaluation of the various approaches. Agreement exists that prisoners are at risk of coercion, which might interfere with their ability to provide voluntary informed consent to research. Controversy exists about the magnitude of this risk and the consequences that should follow from this risk. Two strategies are proposed for a method of protecting prisoners that does not lead to discrimination: first, more caution to assure non-coerced consent and second, restrictions on the type of research. Most regulations stress the importance of the principle of equivalence of healthcare in places of detention as part of an efficient protection against research risks and discrimination.
All the presented approaches have shortcomings. While 'over-use' of prisoners for research as compared to the general population is ethically unjustified, not granting prisoners access to studies beneficial to their own health because of over-strict regulations is equally unjustified. A middle solution should be preferred, one that grants a minimum of protection together with the lowest possible barriers. Research that does not entail a direct benefit for the individual detainee should be restricted to types of research that have a benefit for detainees as a group and that are of low risk. What will ultimately protect prisoners best, while producing the greatest benefit for them, is access to the same healthcare available to members of the community including research as a true option.     

ETHICAL ISSUES IN FORENSIC PSYCHIATRIC RESEARCH ON MENTALLY DISORDERED OFFENDERS

This paper analyses ethical issues in forensic psychiatric research on mentally disordered offenders, especially those detained in the psychiatric treatment system. The idea of a 'dual role' dilemma afflicting forensic psychiatry is more complicated than acknowledged. Our suggestion acknowledges the good of criminal law and crime prevention as a part that should be balanced against familiar research ethical considerations. Research aiming at improvements of criminal justice and treatment is a societal priority, and the total benefit of studies has to be balanced against the risks for research subjects inferred by almost all systematic studies. Direct substantial risks must be balanced by health benefits, and normal informed consent requirements apply. When direct risks are slight, as in register-based epidemiology, lack of consent may be counter-balanced by special measures to protect integrity and the general benefit of better understanding of susceptibility, treatment and prevention. Special requirements on consent procedures in the forensic psychiatric context are suggested, and the issue of the relation between decision competence and legal accountability is found to be in need of further study. The major ethical hazard in forensic psychiatric research connects to the role of researchers as assessors and consultants in a society entertaining strong prejudices against mentally disordered offenders.     

Informed Consent in Health Research: Challenges and Barriers in Low‐and Middle‐Income Countries with Specific Reference to Nepal

Obtaining ‘informed consent’ from every individual participant involved in health research is a mandatory ethical practice. Informed consent is a process whereby potential participants are genuinely informed about their role, risk and rights before they are enrolled in the study. Thus, ethics committees in most countries require ‘informed consent form’ as part of an ethics application which is reviewed before granting research ethics approval. Despite a significant increase in health research activity in low‐and middle‐income countries (LMICs) in recent years, only limited work has been done to address ethical concerns. Most ethics committees in LMICs lack the authority and/or the capacity to monitor research in the field. This is important since not all research, particularly in LMICs region, complies with ethical principles, sometimes this is inadvertently or due to a lack of awareness of their importance in assuring proper research governance. With several examples from Nepal, this paper reflects on the steps required to obtain informed consents and highlights some of the major challenges and barriers to seeking informed consent from research participants. At the end of this paper, we also offer some recommendations around how can we can promote and implement optimal informed consent taking process. We believe that paper is useful for researchers and members of ethical review boards in highlighting key issues around informed consent.     

Epidemiology in protection and prevention against environmental mutagens/carcinogens Examples from occupational medicine

Subjects occupationally exposed to potential mutagens/carcinogens represent the most suitable groups for epidemiological studies aimed at assessing the risk for the individual or the offspring. Several cancer risks to humans have been detected by epidemiological studies performed in occupational settings. Cancer epidemiology studies have been able (a) to identify specific occupations or agents associated with the risk; (b) to verify the results of experimental studies; (c) to test the effectiveness of changes in production or preventive measures in decreasing risks. Reproductive epidemiology has suggested a risk of spontaneous abortions or of malformation in the offspring of workers exposed to some chemicals or occupations, but data are often conflicting due to methodological problems. With the aim of early assessment of risk in mind, the epidemiological use of indicators of exposure or of the early effect of exposure to genotoxic agents is increasingly applied to occupational groups. Cytological monitoring of subjects at risk of occupational cancer of lung or bladder is carried out mainly to diagnose precancerous lesions of target tissues. Cytogenetic methods (chromosome aberrations, SCE, micronuclei) in somatic cells provide a means for detecting early effects of occupational exposure to known or potential mutagens/carcinogens in selected groups of individuals, but their significance is widely debated. Monitoring of urinary mutagenicity, as applied in nurses handling cytostatic drugs, is an example of how an indicator of exposure to genotoxins can be used to evaluate the impact of preventive measures. Among the perspectives, biochemical epidemiology seems to be promising in detecting individuals genetically susceptible to cancer.     

Voluntary Informed Consent in Paediatric Oncology Research

In paediatric oncology, research and treatments are often closely combined, which may compromise voluntary informed consent of parents. We identified two key scenarios in which voluntary informed consent for paediatric oncology studies is potentially compromised due to the intertwinement of research and care. The first scenario is inclusion by the treating paediatric oncologist, the second scenario concerns treatments confined to the research context. In this article we examine whether voluntary informed consent of parents for research is compromised in these two scenarios, and if so whether this is also morally problematic. For this, we employ the account of voluntary consent from Nelson and colleagues, who assert that voluntary consent requires substantial freedom from controlling influences. We argue that, in the absence of persuasion or manipulation, inclusion by the treating physician does not compromise voluntariness. However, it may function as a risk factor for controlling influence as it narrows the scope within which parents make decisions. Furthermore, physician appeal to reciprocity is not controlling as it constitutes persuasion. In addition, framing information is a form of informational manipulation and constitutes a controlling influence. In the second scenario, treatments confined to the research context qualify as controlling if the available options are restricted through manipulation of options. Although none of the influences is morally problematic in itself, a combination of influences may create morally problematic instances of involuntary informed consent. Therefore, safeguards should be implemented to establish an optimal environment for parents to provide voluntary informed consent in an integrated research‐care context.     

Reexamining the categorical exclusion of pediatric participants from controlled human infection trials

Controlled human infection (CHI) models have been developed for numerous pathogens in order to better understand disease processes and accelerate drug and vaccine testing. In the past, some researchers conducted highly controversial CHIs with vulnerable populations, including children. Ethical frameworks for CHIs now recommend vulnerable populations be excluded because they cannot consent to high risk research. In this paper we argue that CHI studies span a wide spectrum of benefit and risk, and that some CHI studies may involve minimal risk. The categorical exclusion of children from CHIs therefore departs from the standard approach to evaluating research risks, as international regulations and ethical guidance for pediatric research generally permit non-beneficial research with low risks. The paradigm in research ethics has also shifted from focusing on protecting vulnerable participants to recognizing that inclusion can be important as a matter of justice, providing new reasons to question this default exclusion of children from CHIs. Recognizing that pediatric CHIs can raise complex ethical issues and are easy to sensationalize in ways that may threaten the public’s trust in research and sponsor institutions, we conclude by describing additional complexities that must be addressed before pediatric CHIs beyond licensed vaccine studies might be ethically acceptable.     

Prevention. How much harm? How much benefit? 4. The ethics of informed consent for preventive screening programs.

Preventive interventions may have few or unproven benefits, or they may even be harmful. Since three of the fundamental precepts of Western biomedical ethics are beneficence, non-maleficence and respect for individual autonomy, failure to obtain truly informed consent for many current preventive interventions may be unethical. However, there are many impediments to obtaining such consent. Physicians need to be aware of an immense amount of up-to-date, complex information. It may be difficult for patients to assimilate this information, and there is rarely time for physicians to become informed and to inform their patients. Clinical practice guidelines may be helpful, but not all are based on evidence, and recommendations are often conflicting. Medical institutions, as well as individual clinicians, can help solve these dilemmas. Authors and journal editors can make a commitment to report and publish well-referenced evidence-based guidelines. Organizations such as the Canadian Task Force on the Periodic Health Examination and the US Preventive Services Task Force can develop balanced, evidence-based patient-information material. Faculty at all levels of medical education can increase their emphasis on the ethics of prevention. Individual clinicians should avoid making clinical decisions on the basis of relative reductions of morbidity or mortality, should use evidence-based clinical practice guidelines rather than those based on authority whenever possible, should make use of patient-information material and, most important, should have a consistent policy of obtaining informed consent from patients before they participate in potentially harmful preventive programs.     

Reducing harm from tobacco smoke exposure during pregnancy

In addition to the health risks that maternal tobacco smoke exposure in pregnancy poses to women, this is a cause of substantial fetal morbidity and mortality. In pregnancy, maternal tobacco smoke exposure can arise because women either smoke or are passively exposed to environmental tobacco smoke as a consequence of other's smoking. This article discusses the scope for clinicians to help reduce both types of tobacco smoke exposure in pregnancy, with a specific focus on available and effective interventions for smoking cessation by pregnant women. Behavioral support with smoking cessation is the only intervention that has been proven to encourage smoking cessation in pregnancy and reduces smoking rates in late pregnancy by 6 to 7%. There are physiological reasons to suspect that nicotine replacement therapy (NRT) will be less or (in)effective for smoking cessation in pregnancy when compared with its use by nonpregnant smokers. However, there are also strong theoretical reasons to suspect that NRT is likely to be safer than continued smoking in pregnancy. Consequently, this article reviews evidence for the safety and effectiveness of NRT when used for smoking cessation in pregnancy and recommendations concerning the use of NRT in pregnancy are presented.     

On the Alleged Right to Participate in High‐Risk Research

Reigning regulatory frameworks for biomedical research impose on researchers and research ethics committees an obligation to protect research participants from risks that are unnecessary, disproportionate to potential research benefits, and non‐minimized. Where the research has no potential to produce results of direct benefit to the subjects and the subjects are unable to give consent, these requirements are strengthened by an additional condition, that risks should not exceed a certain minimal threshold. In this article, I address the question of whether there should be limits of permissible risks in non‐therapeutic research involving competent and healthy subjects. Some commentators argue that competent and informed individuals should have a right to participate even in extremely risky research and that research ethics committees should never reject studies because they are too dangerous. To use David Shaw's expression, competent volunteers should have ‘a right to participate in high‐risk research’. I argue that this idea is ill‐founded, as it does not take into account the social mission and complex collaborative nature of research practice as well as the inequity of power between researchers and subjects. Imposition of limits on permissible risks for healthy volunteers is justified by the need to protect research enterprise and the need to protect the weaker party, namely the subjects. Also, I suggest that the best way to set boundaries on research risks is to leave the judgment of risk acceptability to research ethics committees.     

Lifetime Risk of Fatal Occupational Injuries within Industries,by Occupation,Gender, and Race

Estimates of risk accumulated over a working lifetime are used to assess the significance of many workplace health hazards. Most studies which have estimated this risk have focused on a worker's lifetime risk of dying of a stated illness based on exposure to a hazard in a specific job. The concept, however, has not been widely applied to occupational injury deaths. This study examines the use of lifetime risk based on national fatal injury data from the Bureau of Labor Statistics (BLS) Census of Fatal Occupational Injuries (CFOI). Lifetime risks are defined by specific causal events for those groups identified as having the highest general lifetime risks. The lifetime risk model for injury used in this work can be compared with risk assessments for occupational illnesses. Fatal injury lifetime risk estimates will be useful in defining traumatic injury exposures that are appropriate for targeting research and prevention efforts needed to reduce the burden of work-related death within the United States. These estimates also provide a means of prioritizing traumatic injury research with fatal illness research, while providing the additional benefit of providing a means of informing workers of their fatal injury risks.     

The Impact of Animal Welfare Advertising on Opposition to the Canadian Seal Hunt and Willingness to Boycott the Canadian Seafood Industry

The purpose of this research was to measure and compare the initial and carryover effects of a video advertisement developed by an animal welfare organization, namely Harpseals. org. The ad was designed to educate the public about an egregious act against wildlife (i.e., the Canadian seal hunt), increase opposition to this act, and recruit participation to boycott the industry (i.e., the Canadian seafood industry). After initial opposition to the egregious act had been measured, respondents were exposed to the ad, and subsequently asked again about their opposition to the seal hunt as well as their willingness to join the Canadian Seafood Boycott. About two months later, a follow-up study investigated whether the respondents' opposition to the seal hunt and their participation in the Canadian Seafood Boycott were still affected by the advertisement to which they had been exposed during the first contact. The results show that respondents' level of opposition to the seal hunt—even though it had somewhat leveled off in two months—was still significantly higher (42% higher) than before respondents had been exposed to the advertisement. The results further show that the single exposure to the ad increased boycott participation from 3.1% (as measured in December 2010) to 13.8% (as reported in February/March 2011), an increase of 350%.     

Review: Assessment of dairy cow welfare at pasture: measures available,gaps to address,and pathways to development of ad-hoc protocols

Pasture is generally perceived as positive for dairy cow welfare, but it nevertheless exposes cows to heat, parasites, and other challenges. This review is intended for people ready to design comprehensive protocols for assessing the welfare of dairy cows at pasture. We provide an overview of the benefits and risks of pasture for cows, and then go on to identify the available and feasible measures for assessing cow welfare at pasture and the gaps that need to be addressed to develop specific welfare measures. Some of the measures from on-farm welfare assessment protocols designed for indoor use (e.g. Welfare Quality®) are relevant for cows at pasture (e.g. lameness scoring). However, the timing, location and/or method for certain measures (e.g. observation of social behaviour) need to be adapted to the pasture context, as cows at pasture can roam over a large area. Measures to address specific pasture-related risks (e.g. heat stress, biosecurity) or benefits (e.g. expression of a wide range of behaviours) should be implemented in order to capture all dimensions of cow welfare at pasture. Furthermore, cow welfare is liable to vary over the grazing season due to changes in weather conditions, grass quality and pasture plots that induce variations in lying surface conditions, food availability, distance to walk to the milking parlour, and so on. It is therefore important to investigate the variability in different welfare measures across the pasture season to check whether they hold stable over time and, if not, to determine solutions that can give an overview across the grazing season. Sensors offer a promising complement to animal and environment observations, as they can capture long-term animal monitoring data, which is simply not possible for a one-day welfare-check visit. We conclude that some measures validated for indoor situations can already be used in pasture-based systems, while others need to be validated for their fitness for purpose and/or use in pasture conditions. Furthermore, thresholds should probably be determined for measures to fit with pasture contexts. If all measures can be made adaptable to all situations encountered on farms or variants of the measures can at least be proposed for each criterion, then it should be possible to produce a comprehensive welfare assessment protocol suitable for large-scale use in near future.     

Bioethics for clinicians: 14. Ethics and genetics in medicine

Information about a patient''s inherited risk of disease has important ethical and legal implications in clinical practice. Because genetic information is by nature highly personal yet familial, issues of confidentiality arise. Counselling and informed consent before testing are important in view of the social and psychological risks that accompany testing, the complexity of information surrounding testing, and the fact that effective interventions are often not available. Follow-up counselling is also important to help patients integrate test results into their lives and the lives of their relatives. Genetic counselling should be provided by practitioners who have up-to-date knowledge of the genetics of and the tests available for specific diseases, are aware of the social and psychological risks associated with testing, and are able to provide appropriate clinical follow-up. Some physicians may elect to refer patients for genetic counselling and testing. However, it is inevitable that all physicians will be involved in long-term follow-up both by monitoring for disease and by supporting the integration of genetic information into patients'' lives.